Document Detail

ClC3 is a critical regulator of the cell cycle in normal and malignant glial cells.
MedLine Citation:
PMID:  18784301     Owner:  NLM     Status:  MEDLINE    
Although most brain cells are postmitotic, small populations of progenitor or stem cells can divide throughout life. These cells are believed to be the most likely source for primary brain malignancies including gliomas. Such tumors share many common features with nonmalignant glial cells but, because of their insidious growth, form cancers that are typically incurable. In studying the growth regulation of these tumors, we recently discovered that glioma cell division is preceded by a cytoplasmic condensation that we called premitotic condensation (PMC). PMC represents an obligatory step in cell replication and is linked to chromatin condensation. If perturbed, the time required to complete a division is significantly prolonged. We now show that PMC is a feature shared more commonly among normal and malignant cells and that the reduction of cell volume is accomplished by Cl(-) efflux through ClC3 Cl(-) channels. Patch-clamp electrophysiology demonstrated a significant upregulation of chloride currents at M phase of the cell cycle. Colocalization studies and coimmunoprecipitation experiments showed the channel on the plasma membrane and at the mitotic spindle. To demonstrate a mechanistic role for ClC3 in PMC, we knocked down ClC3 expression using short hairpin RNA constructs. This resulted in a significant reduction of chloride currents at M phase that was associated with a decrease in the rate of PMC and a similar impairment of DNA condensation. These data suggest that PMC is an integral part of cell division and is dependent on ClC3 channel function.
Christa W Habela; Michelle L Olsen; Harald Sontheimer
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  28     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-11     Completed Date:  2008-11-03     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9205-17     Citation Subset:  IM    
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MeSH Terms
Analysis of Variance
Angiogenesis Inhibitors / pharmacology
Animals, Newborn
Cell Cycle / physiology*
Cell Division / physiology
Cell Membrane / metabolism
Cell Size
Cells, Cultured
Chloride Channels / physiology*
Chlorides / metabolism
Computer Simulation
DNA / metabolism
Gene Expression Regulation / drug effects,  physiology
Glioma / pathology,  physiopathology*
Membrane Potentials / drug effects,  physiology
Models, Biological
Neuroglia / cytology,  physiology*
Nitrobenzoates / pharmacology
Patch-Clamp Techniques / methods
Time Factors
Tubulin / metabolism
Grant Support
P30 NS057098/NS/NINDS NIH HHS; P30 NS057098-03/NS/NINDS NIH HHS; P50-CA97247/CA/NCI NIH HHS; R01 NS031234/NS/NINDS NIH HHS; R01 NS031234-14A1/NS/NINDS NIH HHS; R01 NS031234-15/NS/NINDS NIH HHS; R01 NS036692/NS/NINDS NIH HHS; R01 NS036692-08/NS/NINDS NIH HHS; R01 NS036692-09A2/NS/NINDS NIH HHS; R01-NS031234/NS/NINDS NIH HHS; R01-NS036692/NS/NINDS NIH HHS
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Chloride Channels; 0/Chlorides; 0/ClC-3 channel; 0/Nitrobenzoates; 0/Tubulin; 3A35O9G3YZ/5-nitro-2-(3-phenylpropylamino)benzoic acid; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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